BackgroundDiagnosing pancreatic ductal adenocarcinoma (PDAC) in the setting of metastasis with an unknown primary remains very challenging due to the lack of specific biomarkers. HNF-1B has been characterized as an important transcription factor for pancreatic development and was reported as a biomarker for clear cell subtype of PDAC.MethodsTo investigate the diagnostic role of HNF-1B for PDAC, we used tissue microarray (TMA) and immunohistochemistry (IHC) to characterize HNF-1B expression in a large cohort of carcinomas, including 127 primary PDACs, 47 biliary adenocarcinomas, 17 metastatic PDACs, and 231 non-pancreaticobiliary carcinomas.ResultsHNF-1B was expressed in 107 of 127 (84.3%) of PDACs, 13 of 15 (86.7%) of cholangiocarcinomas, 13 of 18 (72%) of ampullary carcinomas, and 13 of 14 (92.9%) of gallbladder adenocarcinomas. Notably, HNF-1B was expressed in 16 of 17 (94.1%) of metastatic PDACs. Among the non-pancreaticobiliary cancers, HNF-1B was expressed in ~ 77% clear cell carcinomas of the kidney and ovarian clear cell carcinomas. Gastroesophageal, lung, and prostate adenocarcinomas occasionally expressed HNF-1B in up to 37% cases. HNF-1B was completely negative in hepatocellular, colorectal, breast, and lung squamous cell carcinomas. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of HNF-1B for primary pancreaticobiliary carcinoma is 84, 68, 66, 85, and 75%, respectively. HNF-1B expression was not significantly associated with overall survival in patients with PDAC, but tumor size ≥2 cm and high tumor grade were significantly associated with worse overall survival in multivariate analyses.ConclusionsHNF-1B may be used in surgical pathology to aid the diagnosis of metastatic pancreatic and biliary carcinoma with a panel of other markers to exclude lung, kidney, prostate, and Müllerian origins.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma with an estimated incidence of less than one per million. Unlike other hematopoietic malignancies, lymphadenopathy and hepatosplenomegaly are uncommon, and patients typically present with nonspecific symptoms. IVLBCL presents a diagnostic challenge and patients are usually diagnosed late in the disease course, if at all, and the prognosis is poor. The differential diagnosis is broad, and physicians often pursue multiple diagnostic possibilities during patient workup. We present a case of IVLBCL discovered at autopsy in an 80-year-old male who presented with history and symptoms pointing to the tick-borne illness ehrlichiosis.

A 21-year-old man presented with immune thrombocytopenic purpura refractory to steroids and intravenous immunoglobulin. Imaging revealed mild splenomegaly without lesions. Laparoscopic splenectomy was performed for refractory thrombocytopenia. Gross examination showed a 250-g spleen without abnormalities. Histologically, a single, well-circumscribed, 2-mm subcapsular lesion with anastomosing vascular channels was identified. The vascular spaces were lined with tall columnar endothelial cells without atypia (panels A and C, hematoxylin and eosin stain; panel A, original magnification 34; panel C, original magnification 350). The lesion was negative for CD8 (panel B; original magnification 34) and CD34 (panel D; original magnification 350) and positive for CD31 (panel E; original magnification 350) and CD163 (panel F; original magnification 350) by immunohistochemistry.Littoral cell angiomas (LCAs) are rare primary vascular neoplasms of the spleen originating from littoral cells that line red pulp sinuses. Unlike normal littoral cells, LCAs are classically negative for CD8. They are often discovered incidentally or the patient may present with abdominal pain, fever, and symptoms of hypersplenism. In this case, it is unlikely that such a small solitary lesion contributed to the patient's thrombocytopenia. Definitive diagnosis requires histologic and immunohistochemical studies after splenectomy. LCAs were originally thought to be benign, but recently, they have been described as having some malignant potential as well as an association with visceral malignancies and immunologic disorders. Given these possibilities, close clinical follow-up is recommended.For additional images, visit the ASH IMAGE BANK, a reference and teaching tool that is continually updated with new atlas and case study images. For more information visit http://imagebank.hematology.org.

Screening for CALR mutations is essential in BCR-ABL-negative MPNs since it not only provides valuable diagnostic and prognostic information but also identifies potential treatment targets. Since this study describes the importance of screening for known and novel biomarkers, we described in detail three methods that could be easily integrated into a clinical laboratory.

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